Chagas disease (ChD) is a tropical disease resulting from parasite infection with an estimated 8 to 14 million chronic cases in Latin America, and has also become a public health concern in the U.S., Europe, and other nonendemic regions. Current treatment for ChD is limited to two drugs, benznidazole and nifurtimox, which have limited efficacy and serious side effects. There is no preventive or therapeutic vaccine for human ChD. Over the years, various groups have developed experimental vaccines, using mainly parasite lysates, purified or recombinant proteins and peptides, and DNA, targeting almost exclusively protein antigens. Most, if not all, of these vaccines have failed to provide protection to animals challenged with different parasite strains.
Patients with acute or chronic Chagas disease (ChD), from diverse geographical locations in Latin America, have very high titers of trypanolytic, protective anti-α-galactosyl antibodies (Ch anti-α-Gal Abs). These antibodies are protective and thought to be the major host immune mechanism controlling parasitemia at both acute and chronic stages of ChD. Ch anti-α-Gal Abs recognize highly immunogenic terminal, non-reducing α-Gal-containing epitopes abundantly expressed on major immunodominant glycoproteins (such as mucins and TS/gp85 glycoproteins) of the mammal-dwelling trypomastigote form. Since these α-Gal epitopes are absent in human cells, it is contemplated that an effective human ChD vaccine is obtained using these immunodominant B-cell epitopes. An α-Gal-based vaccine, however, has thus far been hindered by (a) technical difficulties related to purification, structural analysis, and synthesis of α-Gal-containing glycans; and (b) lack of a suitable animal model that closely mimics the specific human anti-α-Gal response.
There remains a need for therapeutic and preventative compositions for the treatment and characterization of parasitic disease such as Chagas disease.